title: Overexpression of MMP-9 contributes to invasiveness of prostate cancer cell line LNCaP.
abstract: Matrix metallaprotinase-9 (MMP-9) is zinc-containing proteinase whose expression and trafficking are frequently altered in cancer. MMP-9 in the plasma membrane and the secreted forms are thought to contribute to the invasive and metastatic properties of malignant tumors. We have manipulated the expression of MMP-9 in prostate tumor cell line LNCaP and measured their capacity to invade through a basement membrane matrix. Stable expression of human MMP-9 in a poorly metastatic LNCaP prostate cancer cell line produced a 2-3-fold increase in MMP-9 activity and a comparable increase in invasiveness. Transient transfection of LNCaP stable clone expressing MMP-9 with MMP-9 antisense oligonucleotide (ASODN) produced 55-90% less MMP-9 than control cells and were proportionately less invasive. In contrast, manipulating MMP-9 levels had no effect on cell migration across an uncoated membrane. A standard MMP-9 inhibitor at a concentration ranging from 1-10 nM, caused a nearly quantitative inhibition of extracellular MMP-9 activity and had significant effect on basement membrane invasion. Collectively, these results confirm the role of MMP-9 in tissue remodeling associated with prostate tumor invasion.
authors.affiliation: Department of Medicine, Division of Allergy, Immunology and Rheumatology, State University of New York at Buffalo and Buffalo General Hospital, Kaleida Health, New York 14203, USA. ra5@buffalo.edu
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Aalinkeel
authors.forename: Bindukumar B
authors.initials: BB
authors.lastname: Nair
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Reynolds
authors.forename: Donald E
authors.initials: DE
authors.lastname: Sykes
authors.forename: Supriya D
authors.initials: SD
authors.lastname: Mahajan
authors.forename: Kailash C
authors.initials: KC
authors.lastname: Chadha
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Schwartz
mesh_terms: D001485:Basement Membrane / Q000473:pathology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics*
chemical_list: D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D016376:Oligonucleotides, Antisense; D020780:Matrix Metalloproteinase 9